Inclusion Criteria:

          1. Histologically confirmed diagnosis of colorectal adenocarcinoma

          2. Any RAS mutation that prevent treatment with anti-EGFR antibodies

          3. Stage IV

          4. Measurable disease according to RECIST v. 1.1

          5. Disease progression during or following a treatment with fluoropyrimidine, oxaliplatin
             and bevacizumab, and a treatment with irinotecan is not considered immediately
             mandatory by the Investigator

          6. Age ≥ 18 years

          7. ECOG Performance Status 0-1

          8. Neutrophils > 1500 / mm3, platelets > 100,000 / mm3, and hemoglobin > 9 g/dL without
             transfusion or granulocyte-colony stimulating factor (G-CSF) and other hematopoietic
             growth factors.

          9. Bilirubin level < 1.5 x ULN

         10. Glomerular filtration rate > 30 mL/min/1.73 m2 according to the Modified Diet in Renal
             Disease abbreviated formula

         11. AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN (≤ 5 x ULN if liver metastasis are present)

         12. Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN if liver metastasis are present)

         13. Serum creatinine < 1.5 x ULN

         14. Amylase and lipase ≤ 1.5 x ULN

         15. INR and aPTT ≤ 1.5 x ULN. Subjects who are therapeutically treated with an agent such
             as warfarin or heparin will be allowed to participate if no underlying abnormality in
             coagulation parameters exists per medical history.

         16. Understand, be willing to give consent, and sign the written informed consent form
             (ICF) prior to undergoing any study-specific procedure.

         17. If female and of childbearing potential, have a negative result on a pregnancy test
             performed a maximum of 7 days before initiation of study treatment.

         18. If potentially childbearing female, or if male, agree to use adequate contraception
             (eg, abstinence, intrauterine device, oral contraceptive, or double-barrier method)
             from the date on which the ICF is signed until 8 weeks after the last dose of study
             drug.

         19. Life expectancy of greater than 3 months

        Exclusion Criteria:

          1. Previous treatment with regorafenib or irinotecan

          2. Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir,
             itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir,
             saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine,
             phenobarbital, phenytoin, rifampin, St. John's Wort)

          3. Have had a major surgical procedure, open biopsy, or significant traumatic injury
             within 28 days prior to initiation of study treatment

          4. Have congestive heart failure classified as New York Heart Association Class 2 or
             higher

          5. Have had unstable angina (angina symptoms at rest) or new-onset angina < 3 months
             prior to screening.

          6. Have had a myocardial infarction < 6 months prior to initiation of study treatment.

          7. Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta
             blockers or digoxin.

          8. Have had arterial or venous thrombotic or embolic events such as cerebrovascular
             accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary
             embolism within 6 months prior to the initiation of study treatment

          9. Symptomatic brain metastases or meningeal tumors

         10. Patients with evidence or history of bleeding diathesis

         11. Uncontrolled hypertension (systolic blood pressure [SBP] >140 mmHg or diastolic blood
             pressure [DBP] > 90 mmHg)

         12. Have interstitial lung disease with ongoing signs and symptoms at the time informed
             consent is obtained

         13. Have persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine
             ratio from a random urine sample (< Grade 3, CTCAE v 4.0).

         14. Have unresolved toxicity higher than National Cancer Institute-Common Terminology for
             Adverse Events version 4.0 (CTCAE v 4.0) Grade 1 attributed to any prior
             therapy/procedure, excluding alopecia and/or oxaliplatin-induced neurotoxicity ≤ Grade
             2 and hemoglobin ≥ 9 g/dL as per inclusion criteria

         15. Patients who cannot take oral medication, who require intravenous alimentation, have
             had prior surgical procedures affecting absorption, or have active peptic ulcer
             disease

         16. Pregnant or lactating women

         17. Any other malignancies within 5 years (except for adequately treated carcinoma in situ
             of the cervix or non melanoma skin cancer)

         18. Any unstable systemic disease (including active infections, any significant hepatic,
             renal or metabolic disease), metabolic dysfunction, physical examination finding, or
             clinical laboratory finding that contraindicates the use of regorafenib or render the
             patient at high risk for treatment complications

         19. Sexually active males and females (of childbearing potential) unwilling to practice
             contraception during the study.

         20. Have any other serious or unstable illness, or medical, psychological, or social
             condition, that could jeopardize the safety of the subject and/or his/her compliance
             with study procedures, or may interfere with the subject's participation in the study
             or evaluation of the study results.

         21. Have a known hypersensitivity to any of the study drugs, study drug classes, or
             excipients in the formulation of the study drugs.

         22. Have a close affiliation with the investigational site (eg, be a close relative of the
             investigator) or be a dependent person (eg, be an employee or student working at the
             investigational site).