Study to Evaluate the Efficacy of FOLFOX + Panitumumab Followed by FOLFIRI + Bevacizumab (Sequence 1) Versus FOLFOX + Bevacizumab Followed by FOLFIRI + Panitumumab (Sequence 2) in Untreated Patients With Wild-type RAS Metastatic, Primary Left-sided, Unresectable Colorectal Cancer

Inclusion Criteria:

1. Man or woman at least 18 years old.

2. Capable of understand, sign and date an informed consent approved by an IEC.

3. Histologically confirmed adenocarcinoma of the left colon or rectum (originate inthe splenic flexure, descending colon, sigmoid colon, or rectum) in patients withunresectable (not amenable to radical surgery of metastases at the study inclusion)metastatic (M1) disease.

4. Patients who had wild-type RAS status confirmed as per standard of care according tointernational guidelines prior to first-line initiation.

*RAS analysis should include at least KRAS exons 2, 3 and 4 (codons 12, 13, 59, 61, 117 and 146) and NRAS exons 2, 3 and 4 (codons 12, 13, 59, 61 and 117)

5. At least one unidimensionally measurable lesion per RECIST criteria (version 1.1).

6. ECOG performance status < 2.

7. Adequate bone marrow function: neutrophils ≥1.5 x109 / L; platelets ≥100 x109 /L;haemoglobin ≥ 9 g/dL.

8. Hepatic, renal and metabolic function as follows:

• Total bilirubin count ≤1.5 x upper limit of normal (ULN), serum glutamicpyruvic transaminase/alanine aminotransferase (SGPT/ALT) and serum glutamicoxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) ≤ 2.5 x ULN (5 xULN for subjects with liver involvement of their cancer or 10 x ULN forsubjects with bone involvement).

• Renal function, calculated as creatinine clearance or 24-hour creatinineclearance ≥ 50 mL/min.

Exclusion Criteria:

1. History of prior or concurrent central nervous system metastases.

2. History of another primary cancer, except: curatively treated in situ cervicalcancer, or curatively resected non-melanoma skin cancer, or other primary solidtumour curatively treated with no known active disease present and no treatmentadministered for ≥ 5 years before randomization.

3. Prior chemotherapy or other systemic anticancer therapy for treatment of metastaticcolorectal carcinoma.

4. Prior adjuvant chemotherapy for colorectal cancer (stage I, II or III) terminatedless than 6 month before metastatic disease was diagnosed.

5. Unresolved toxicities of a previous systemic treatment that, in the opinion of theInvestigator, cause the patient unfit for inclusion.

6. Prior use (as monotherapy or adjuvant treatment) of anti-EGFR antibody therapy (e.g.cetuximab), anti-VEGF or small molecule EGFR inhibitors (e.g. erlotinib).

7. Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins ≤ 30 days before inclusion.

8. Significant cardiovascular disease including unstable angina or myocardialinfarction within 12 months before initiating study treatment or a history ofventricular arrhythmia.

9. Uncontrolled hypertension.

10. History of interstitial pneumonitis or pulmonary fibrosis or evidence ofinterstitial pneumonitis or pulmonary fibrosis on baseline chest computerisedtomography (CT).

11. Treatment for systemic infection within 14 days before the start of study treatment.

12. Acute or subacute intestinal occlusion and/or active inflammatory bowel disease orother bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoeaaccording to NCI-CTCAE version 4.03).

13. Clinically significant peripheral sensory neuropathy.

14. Evidence of previous acute hypersensitivity reaction, of any grade, to any componentof the treatment.

15. History of Gilbert disease or known dihydropyrimidine deficiency syndrome.

16. Recent (within 6 months before the start of study treatment) gastroduodenal ulcer tobe active or uncontrolled.

17. Recent (within 6 months before the start of study treatment) pulmonary embolism,deep vein thrombosis, or other significant venous event.

18. Pre-existing bleeding diathesis and/or coagulopathy with exception ofwell-controlled anticoagulation therapy (within 6 months before the start of studytreatment)

19. Recent (within 4 weeks prior to inclusion in the study) major surgical procedure,open biopsy, or significant traumatic injury not yet recovered from prior majorsurgery

20. History of any disease that may increase the risks associated with studyparticipation or may interfere with the interpretation of study results.

21. Known positive test for human immunodeficiency virus infection, hepatitis C virus,and chronic active hepatitis B infection.

22. Any disorder that compromises the patient's ability to provide written informedconsent and/or comply with study procedures.

23. Any investigational agent within 30 days prior to inclusion.

24. Pregnant or breastfeeding woman.

25. Surgery (excluding diagnostic biopsy or placement of a central venous catheter)and/or radiotherapy within 28 days prior to inclusion in the study.

26. Male or female of childbearing age who do not agree with taking adequatecontraceptive precautions, i.e. use contraception double barrier (e.g. diaphragmplus condoms) or abstinence during the course of the study and for 6 months afterthe last administration of study drug for women and 1 month for men.

27. The patient is unwilling or unable to meet the requirements of the study.

28. Psychological, geographical, familial or sociological conditions that potentiallyprevent compliance with the study protocol and follow-up schedule.