TAS-102, Irinotecan, and Bevacizumab for the Treatment of Pre-treated Metastatic or Unresectable Colorectal Cancer, the TABAsCO Study

Inclusion Criteria:

• Advanced colorectal cancer (metastatic or unresectable): Histologically orcytological proven adenocarcinoma of the colon or rectum which is metastatic orotherwise incurable

• Prior treatment with a fluoropyrimidine (5-fluorouracil [5-FU] or capecitabine) andoxaliplatin in the metastatic/unresectable setting OR, recurrence within 12 monthsof adjuvant therapy with a regimen that included oxaliplatin

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Hemoglobin >= 9 g/dL

• Absolute neutrophil count >= 1500/mm^3

• Platelet count >= 100,000/mm^3

• Creatinine < 1.5 upper limit of normal (ULN) or if >= 1.5 x ULN creatinine clearance (CRCL) >= 30 mL/min (by Cockcroft-Gault)

• Bilirubin < 1.5 x ULN

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5x ULN if with hepatic metastases

• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present

• Participants of child-bearing potential must agree to use adequate contraceptivemethods (e.g., hormonal or barrier method of birth control; abstinence) prior tostudy entry. Should a woman become pregnant or suspect she is pregnant while she orher partner is participating in this study, she should inform her treating physicianimmediately

• Participant must understand the investigational nature of this study and sign anIndependent Ethics Committee/Institutional Review Board approved written informedconsent form prior to receiving any study related procedure

Exclusion Criteria:

• Prior treatment with TAS-102 or irinotecan

• Anti-cancer therapy within 2 weeks of the planned first dose of study medication

• Unresolved toxicities from prior therapy of > grade 1, excluding alopecia or similartoxicities which are not deemed to be clinically significant or put the participantat greater risk. Grade 2 neuropathy is permitted

• Major surgery within 4 weeks of anticipated start of therapy

• Uncontrolled hypertension: systolic blood pressure >= 150, diastolic blood pressure >= 100

• Unstable angina, symptomatic congestive heart failure or cardiac arrhythmiarequiring anti-arrhythmic therapy (beta-blockers, calcium channel blockers anddigoxin are allowed)

• Arterial or venous thrombotic or embolic events within 3 months of study initiation,unless well controlled on stable anti-coagulation for >= 2 weeks. This excludesuncomplicated catheter associated venous thrombosis

• History of cerebrovascular or myocardial ischemia within 6 months of initiation

• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 grade 3 or greater hemorrhage within the past 4 weeks

• Proteinuria >= 2+, unless 24 hour urine collection demonstrates =< 1 g of protein ORspot protein: creatinine demonstrates a ratio of =< 1

• Untreated brain metastases

• History of abnormal glucuronidation of bilirubin (Gilbert's syndrome)

• History of second primary malignancy within 3 years prior to enrollment, excludingin-situ cervical carcinoma, non-melanoma skin cancer or malignancy of equivalentrisk which is highly unlikely to require systemic treatment in the next 2 years

• Have known active infection which would heighten the risk of complications

• Pregnant or nursing female participants

• Unwilling or unable to follow protocol requirements

• Any condition which in the investigator's opinion deems the participant anunsuitable candidate to receive study drug