Study to Determine the Efficacy of Regorafenib in Metastatic Colorectal Cancer Patients and to Discover Biomarkers

Inclusion Criteria: 1. Signed informed consent. 2. Age ≥18 years. 3. Histological documentation of adenocarcinoma of the colon or rectum, with at least one liver metastatic site available for biopsy. 4. Metastatic disease not suitable for upfront curative-intent surgery. 5. Patients must have received one (and no more than one) prior treatment regimen for metastatic CRC. 6. Measurable disease according to RECIST v.1.1. 7. ECOG status ≤1. 8. Life expectancy ≥ 3 months. 9. Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. 10. Adequate bone-marrow, liver, and renal function: * Total bilirubin ≤1.5 × ULN * ALT and AST ≤5 × ULN (since liver involvement of their cancer) * Alkaline phosphatase limit ≤5 × ULN, since liver involvement of their cancer * Amylase and lipase ≤1.5 × ULN * Serum creatinine ≤1.5 × ULN * INR and PTT ≤1.5 × ULN. * Platelet count ≥100 x 10\^9/L, hemoglobin ≥90 g/L, absolute neutrophil count (ANC) \>1.5 x 10\^9/L Exclusion Criteria: 1. Previous treatment with regorafenib. 2. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years before randomization, EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumours. 3. Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities. The site of irradiation should have evidence of progressive disease (new lesions or increase in lesion size) if this is the only site of disease. 4. Major surgical procedure or significant traumatic injury within 28 days before starting the study treatment. 5. Female patients that are pregnant or breast-feeding. 6. Congestive heart failure ≥ Class 2 according to the NYHA. 7. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug 8. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). 9. Uncontrolled hypertension 10. Phaeochromocytoma 11. Pleural effusion or ascites that causes respiratory compromise. 12. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 3 months before starting the study treatment. 13. Ongoing uncontrolled infection \> Grade 2 per CTCAE v. 4.0. 14. Known history of HIV infection. 15. Active hepatitis B or C, or chronic hepatitis B or C requiring antiviral therapy. 16. Seizure disorder requiring medication. 17. Any history of or currently known brain metastases (patients with stable brain metastases ≥ 3 months may be eligible for the study). 18. History of organ allograft. 19. Evidence or history of severe bleeding diathesis. 20. Non-healing wound, ulcer, or bone fracture. 21. Renal failure requiring haemodialysis or peritoneal dialysis 22. Dehydration ≥ 2 per CTCAE v. 4.0. 23. Substance abuse or medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. 24. Known hypersensitivity to regorafenib, regorafenib class of drugs, or excipients in the formulation. 25. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient in the opinion of the investigator. 26. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent. 27. Persistent proteinuria ≥ Grade 3 per CTCAE v. 4.0 (i.e. \>3.5g/24 hours). 28. Inability to swallow oral medications. 29. Any malabsorption condition. 30. Unresolved toxicity \> Grade 1, attributed to any prior therapy/procedure, excluding alopecia and oxaliplatin neurotoxicity ≤ Grade 2, per CTCAE v. 4.0.