Second-line FOLFOX With or Without Regorafenib in mCRC Patients Failed to First-line Irinotecan Plus Fluoropyrimidines

Inclusion Criteria: 1. Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum. 2. Progressed during or within 6 months of first-line irinotecan plus fluoropyrimidines with or without targeted agents (bevacizumab or cetuximab). 3. Measurable or evaluable lesion(s) by RECIST 1.1. 4. Unresectable metastatic disease. 5. Age over 20 years old. 6. ECOG performance status of 1 or lower. 7. Adequate organ functions. A. Bone marrow function: ANC ≥ 1,500/mm3, platelet ≥ 100,000/mm3 B. Hepatic functions: bilirubin ≤ 1.5 X ULN, AST/ALT ≤ 2.5 X ULN (≤ 5 X ULN in cases of liver metastasis) C. Renal functions: serum Cr ≤ 1.5 X ULN or calculated CCr (Cockroft) ≥ 60 ml/min 8. Be willing and able to comply with the protocol for the duration of the study. 9. Give written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw the study at any time, without prejudice. 10. Women of childbearing potential and men must agree to use adequate contraception since signing of the IC form until at least 8 weeks after the last study drug administration. Exclusion Criteria: 1. Prior treatment of regorafenib. 2. Prior exposure to oxaliplatin as metastatic setting is not allowed in any case; however, prior exposure to oxaliplatin as (neo)adjuvant chemo(radio)therapy is allowed if progressed after 12 months from the date of completion of oxaliplatin-containing (neo)adjuvant treatment. 3. Concurrent or previous history of another primary cancer within 3 years prior to randomisation except for curatively treated cervical cancer in situ, non-melanomatous skin cancer, superficial bladder cancer (pTis and pT1) and curatively treated thyroid cancer of any stage. Concurrent, histologically confirmed, unresected thyroid cancer without distant metastasis could be allowed with the agreement of the chief principal investigator. 4. Uncontrolled CNS metastases. 5. Prior radiation therapy would be permitted, but non-radiated evaluable lesions should be present at study entry. 6. Radiation therapy during chemotherapy is not permitted, but if the local investigator decides that radiation therapy should be given during study treatments, he should be convinced that there is no evidence of disease progression with agreement of the chief principal investigator. Radiation therapy during the chemotherapy-free interval between 1st and 2nd line chemotherapy is permitted. 7. Uncontrolled hypertension (\>150/100 mmHg) despite of optimal management; anti-hypertensive drugs for BP lowering before study entry would be permitted. 8. Congestive heart failure ≥ New York Heart Association (NYHA) class 2. 9. Unstable angina, new-onset angina within 3 months, or history of myocardial infarction within 6 months before the study entry. 10. Arterial or venous thromboembolism within 6 months. 11. Serious concurrent infections or non-malignant illness. 12. Liver cirrhosis ≥ Child-Pugh class B. 13. Prior unanticipated severe toxicity to fluoropyrimidines, or known dihydropyrimidine dehydrogenase (DPD) deficiency. 14. Prior hypersensitivity to oxaliplatin (grade ≥ 2). 15. Peripheral neuropathy of grade ≥ 2. 16. Major surgery or significant traumatic injury within 28 days prior to study treatment. 17. Non-healing wound, ulcer, or bone fracture. 18. Current evidence of significant gastrointestinal bleeding or (impending) obstruction. 19. Proteinuria ≥ 3+ in the routine urinalysis; in this case, the total protein in the 24-hour urine collection should be measured, and the accrual is permitted if total protein \< 3.5 g/day. 20. Concomitant participation in another clinical trial. 21. Pregnant of breast-feeding subjects. Women of child-bearing potential must have pregnancy test within 7 days and a negative result must be documented before start of study treatment. 22. Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.