Inclusion Criteria:

          1. Provision of signed and dated informed consent and stated willingness to comply with
             all study procedures and availability for the duration of the study, Signed, written
             Informed Consent Form (ICF),

          2. Willing and able to comply with the protocol,

          3. Age 18-75 years,

          4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1,

          5. Life expectancy ≥ 3 months,

          6. Histologically proven carcinoma of colon and/or rectum,

          7. Confirmed unresectable metastatic disease,

          8. At least one measurable and/or evaluable tumor metastasis on CT-scan or MRI per RECIST
             criteria version 1.1,

          9. Prior oxaliplatin-based first-line therapy for metastatic disease (the use of prior
             bevacizumab or anti-EGFR mabs is allowed but not mandatory) - Less than 6 months from
             completion of any prior oxaliplatin-based adjuvant therapy can be considered as
             first-line therapy. Prior use of irinotecan in combination with oxaliplatin and 5FU as
             first-line therapy is allowed if the interval between the last administration of
             irinotecan and disease progression is at least 6 months (ie, irinotecan-free interval
             ≥6 months).

         10. Negative urine and/or serum pregnancy test within 7 days before inclusion if female
             subject is of childbearing potential,

         11. Clinical laboratory parameters adequate as follows:

               -  Serum total bilirubin level ≤ 1.5 x upper normal limit (UNL),

               -  Neutrophil count ≥ 1.5x109/L,

               -  Platelet count ≥ 100x109/L,

               -  Hemoglobin ≥ 9 g/dL,

               -  Serum creatinine level ≤ 150µM,

               -  Serum albumin ≥ 25 g/L,

               -  Calcium ≥ 1 x ULN

               -  Alkaline phosphatase (ALP) < 3 x ULN, alanine aminotransferase (ALT) and
                  aspartate aminotransferase (AST) < 3 x ULN (in the case of liver metastases, <5 x
                  ULN),

               -  Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour,

         12. For women of childbearing potential and for men, agreement to use an effective
             contraceptive method from the time of screening throughout the study until 6 months
             after administration of the last dose of any study medication. Highly effective
             contraceptive method consist of prior sterilization, inter-uterine device,
             intrauterine hormone-releasing system, oral or injectable contraceptives barrier
             methods, and/or true sexual abstinence),

         13. Affiliation to French health care system.

        Exclusion Criteria:

          1. History of arterial thrombotic event in the last 6 months (eg., myocardial infarction,
             cerebrovascular accident or transient ischemic attack),

          2. Uncontrolled hypertension (defined as systolic blood pressure > 140 mmHg and/or
             diastolic blood pressure > 90 mmHg despite optimal medical therapy), or history of
             hypertensive crisis, or hypertensive encephalopathy,

          3. Prior use of aflibercept,

          4. Adverse events from prior anticancer therapy grade ≥2 (National Cancer Institute
             Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0), except for
             neuropathy and alopecia,

          5. Bowel obstruction, inflammatory bowel disease

          6. Known DPD deficiency. If not known for the patient, testing for DPD should be done
             during the screening period (patients with uracilemia ≥16ng/mL are not eligible),

          7. Known UGT1A1 deficiency (eg, Gilbert syndrome, Crigler-Najjar syndrome). If not known
             for the patient, genetic testing for UGT1A1 should be done during the screening period
             for patients with hyperbilirubinemia (ie, total bilirubin level >1xULN),

          8. Active infection requiring intravenous antibiotics at the start of study treatment,

          9. Known active infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or
             hepatitis C (HCV),

         10. Known allergy or hypersensitivity to the active substance or ingredients of any study
             drug,

         11. Women currently pregnant or breastfeeding,

         12. Inability to comply with study and follow-up procedures as judged by the Investigator,

         13. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted
             therapy, immunotherapy)

         14. Concomitant use of Saint John Wort herb (millepertuis), Yellow Fever vaccine, Live
             Attenuated Vaccines (LAV) and phenytoine

         15. Treatment with any other investigational medicinal product within 28 days or 5
             investigational agent half-lives (whichever is longer) prior to the start of study
             treatment,

         16. Any other disease, active, uncontrolled bacterial, viral or fungal infection requiring
             systemic therapy, metabolic dysfunction, physical examination finding or clinical
             laboratory finding that leads to reasonable suspicion of a disease or condition that
             contraindicates the use of study drugs that may affect the interpretation of the
             results, or that may render the subject at high risk for treatment complications.

         17. Previous or concurrent malignancy, except for adequately treated basal or squamous
             cell skin cancer, in situ cervical cancer, or other cancer for which the patient has
             been disease-free for three years prior to study entry,

         18. Surgical procedure (including open biopsy, surgical resection, wound revision, or any
             other major surgery involving entry into a body cavity) or significant traumatic
             injury within 28 days prior to start of study treatment, or anticipation of need for
             major surgical procedure during the course of the study.

         19. Minor surgical procedure including placement of a vascular access device, within 2
             days of start of study treatment,

         20. History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal
             abscess or active GI bleeding within 6 months prior to start study treatment.

         21. Clinically significant active cardiac disease (including NYHA class III or IV
             congestive heart failure)

         22. Venous thromboembolic event (including pulmonary embolism) grade 3 or 4 within 6
             months prior to start study treatment.