CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC

Inclusion Criteria: 1. Personal written informed consent is obtained after the study has been fully explained 2. Histologically confirmed colon or rectal adenocarcinoma \*Excluding appendix cancer and anal canal cancer 3. Clinically unresectable 4. ≥20 years of age at enrollment 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 (≥71 years of age: PS score of 0) 6. Measurable lesion according to RECIST ver. 1.1 criteria on contrast-enhanced chest, abdominal, or pelvic (trunk) CT (required within 28 days of enrollment) 7. No previous chemotherapy for colon or rectal cancer \*Patients with confirmed relapse ≥24 weeks after completion of post-operative adjuvant chemotherapy can be enrolled 8. Ras/Braf mutation analysis at enrollment identifies Ras/Braf status as either the wild type or mutant type. 9. Vital organ functions meet the following criteria within 14 days before enrollment. If multiple test results are available in that period, the results closest to enrollment will be used. No blood transfusions or hematopoietic factor administration will be permitted within 2 weeks before the date on which measurements are taken. i. Neutrophil count: ≥1,500 /cu.mm ii. Platelet count: ≥10.0 × 104/cu.mm iii. Hemoglobin concentration: ≥9.0 g/dL iv. Total bilirubin: ≤1.5 times upper limit of normal (ULN) v. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP): ≤2.5 times ULN (≤5 times ULN for metastases to liver) vi. Serum creatinine: ≤1.5 times ULN, or creatinine clearance: ≥30 mL/min vii. Urine protein: ≤2+ (if ≥3+, urine protein/creatinine ratio: \<2.0) 10. UGT1A1 polymorphism is wild type or single heterozygous type - Exclusion Criteria: 1. Previous radiation therapy in which ≥20% bone marrow was exposed to the radiation field 2. Untreated brain metastases, spinal cord compression, or primary brain tumor 3. History of central nervous system (CNS) disease (excluding asymptomatic lacunar infarction) 4. Continuous systemic corticosteroid treatment is required 5. Oral or parenteral (such as low molecular weight heparin) anticoagulant dose is not consistently (≥14 days) controlled. (Oral anticoagulants: conditions at high risk for bleeding, such as prothrombin time (PT)-international normalized ratio (INR) ≥3, clinically significant active bleeding (within 14 days of enrollment)) 6. Evidence of cardiovascular disease, cerebrovascular disorder (within 24 weeks), myocardial infarction (within 24 weeks), unstable angina pectoris, New York Heart Association (NYHA) classification ≥Grade II congestive heart failure, serious arrhythmias requiring drug therapy 7. Previous treatment with an investigational drug within 28 days prior to enrollment, or participation in a study of an unapproved drug 8. Any of the following comorbidities i. Uncontrolled hypertension ii. Uncontrolled diabetes mellitus iii. Uncontrolled diarrhea iv. Peripheral sensory neuropathy (≥Grade 1) v. Active peptic ulcer vi. Unhealed wound (except for suturing associated with implanted port placement) vii. Other clinically significant disease (such as interstitial pneumonia or renal impairment) 9. Major surgical procedure within 28 days prior to study treatment initiation (such as open chest, laparoscopy, thoracoscopic surgery, laparoscopic surgery), unless only colostomy is performed; open biopsy or suturing for major trauma within 14 days of study treatment initiation; or planned major surgical procedure during the study (open chest, laparoscopy) ("major surgical procedures" does not include central venous (CV) port insertion) 10. Physical defects of the upper gastrointestinal tract; malabsorption syndrome or difficulty taking oral medication 11. Pregnant, breastfeeding, positive pregnancy test (women who have menstruated in the last year will be tested), or women who are unwilling to use contraception; men who are unwilling to use contraception during the study 12. Active hepatitis B or C, or evidence of HIV infection 13. Previous chemotherapy for other malignancies (excluding hormone therapy for breast cancer) 14. Other active malignancies (synchronous malignancies, and asynchronous malignancies separated by a 5-year disease-free interval) (excluding malignancies that are expected to be completely cured, such as intramucosal carcinoma and carcinoma in situ) 15. Uncontrolled venous thromboembolism (unless clinically stable, asymptomatic, or appropriately treated with an anticoagulant) 16. Arterial thrombosis or arterial thromboembolism such as myocardial infarction, transient ischemic attack, or cerebrovascular attack in the last year prior to enrollment 17. Complications such as intestinal paralysis, intestinal obstruction, or gastrointestinal perforation, current or within 1 year prior to enrollment 18. Pleural effusion, ascites, or pericardial effusion requiring drainage 19. History of hypersensitivity to fluorouracil, levofolinate, oxaliplatin, irinotecan, bevacizumab and their excipients or Chinese hamster ovary cell proteins 20. History of adverse reactions to fluoropyrimidine drugs indicative of dihydropyrimidine dehydrogenase (DPD) deficiency 21. Systemic treatment required for, or evidence of, infections 22. Endoluminal stenting 23. Otherwise unsuitable for the study in the opinion of investigators -