The primary purpose of this study is to determine the non-inferiority of overall survival FOLFIRI with or without Bevacizumab compared with Irinotecan (CPT-11) with or without Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.

Primary endpoint: Progression-free survival (PFS)； Secondary endpoints: Overall survival (OS), Time to treatment failure (TTF), Overall response rate (ORR), Disease Control Rate (DCR), Safety.

Inclusion Criteria:

1. Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer.
2. Age ≥18 years at the time of informed consent
3. ECOG performance status (PS) of 0-2
4. Written informed consent prior to study-specific screening procedures
5. Life expectancy of at least 90 days
6. Withdrawal from first-line chemotherapy (regardless of containing molecular-targeted drugs) for metastatic colorectal cancer due to intolerable toxicity or progressive disease, or relapse within 180 days after the last dose of adjuvant chemotherapy.
7. Adequate organ function according to following laboratory values obtained within 14 days before enrolment (excluding patients who received blood transfusions or hematopoietic growth factors within 14 days before the laboratory test) Neutrophil count: ≥1500/mm3 Platelet count: ≥10.0 x 104/mm3 Hemoglobin: ≥9.0 g/dL Total bilirubin: ≤1.5 mg/dL AST, ALT: ≤100 IU/L (≤200 IU/I if liver metastases present) Serum creatinine: ≤1.5 mg/dL

Exclusion Criteria:

1. History of other malignancy with a disease-free interval <5 years (other than curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic mucosal resection)

2. With massive pleural effusion or ascites requiring intervention

3. Radiological evidence of brain tumor or brain metastases

4. Active infection including hepatitis

5. Any of the following complication:

   i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic ileus) ii) Symptomatic heart disease (including unstable angina, myocardial infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv) Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily activities despite adequate therapy)

6. Any of the following medical history:

   Myocardial infarction: History of one episode within one year before enrollment or two or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii) History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine dehydrogenase (DPD) deficiency

7. Previous treatment with irinotecan hydrochloride

8. Current treatment with atazanavir sulfate

9. Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days before enrollment

10. Pregnant or lactating females, and males and females unwilling to use contraception

11. Requires continuous treatment with systemic steroids

12. Psychiatric disability that would preclude study compliance

13. Otherwise determined by the investigator to be unsuitable for participation in the study

14. Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment

15. History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.

16. History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment

17. Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture

18. Current or recent (within 1 year) thromboembolism or cerebrovascular disease

19. Currently receiving or requires anticoagulation therapy (> 325 mg/day of aspirin)

20. Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)

21. Uncontrolled hypertension

22. Urine dipstick for proteinuria >+2