In patients in progression after oxaliplatin and irinotecan, the study FOLFIRINOX 3 proposes to evaluate the interest of modifying the standard pattern of administration of the molecule of irinotecan in order to make it more efficient. In combination with other chemotherapy drugs (5-fluorouracil, oxaliplatin, folinic acid and bevacizumab), irinotecan will be administered at the beginning and end of each cycle of chemotherapy, whereas it is normally administered at one time in the regimen. standard of treatment.

The hypothesis of this study is an increase in the objective response rate at 2 months of 10 to 30% with a scheme by FOLFIRINOX3 - bevacizumab compared to an optimal treatment to date by FOLFIRINOX-bevacizumab.

Primary objective

• Main objective of phase I: To evaluate the acute toxicity of treatment with FOLFIRINOX 3 - bevacizumab
• Main objective of phase II: To evaluate the efficacy of treatment with FOLFIRINOX 3 - bevacizumab in terms of objective response according to the RECIST criteria.

Secondary objectives

• To evaluate the efficacy of treatment with FOLFIRINOX 3 - bevacizumab in terms of objective response according to the criteria of CHOI, progression-free survival (PFS) and overall survival (OS)
• To evaluate the late toxicity of treatment with FOLFIRINOX 3 - bevacizumab
• Evaluate the quality of life

Inclusion Criteria:

1. Men or women

2. Age ≥ 18 years

3. Performance status of 0 or 1 (WHO ECOG Index)

4. Patient with metastatic colon cancer

5. History of chemotherapy treatment including oxaliplatin, irinotecan, antiangiogenic (bevacizumab or aflibercept) and anti-EGFR if indicated

6. Patient eligible for treatment with FOLFIRINOX bevacizumab

7. Tumor evaluation (thoraco-abdominopelvic CT scan) performed within 4 weeks before inclusion with at least one measurable lesion according to RECIST criteria 1.1

8. Patient able and able to abide by the protocol throughout the study, including treatment, visits, scheduled examinations and follow-up.

9. Biological values within the following limits:

   • Bilirubinemia ≤ 1.5 times the upper limit of normal (N)
   • ASAT and ALAT ≤ 5 N
   • Creatinine ≤ 1.5 N and creatinine clearance> 60 mlmin
   • Neutrophils ≥ 1.5. 109 / L
   • Platelets ≥ 150. 109 / L
   • Hemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused).
   • Albuminémie≥30g / L
   • Hepatitis B, C and HIV negative serologies

10. Information note given and signed informed consent

11. Patient affiliated to a social security scheme

12. Women must have effective contraception and must have a negative pregnancy test at the time of entry into the study or must no longer be of childbearing age (ie, postmenopausal, after 60 years and no menstruation for ≥1 year without any other medical cause, OR history of hysterectomy, OR history of bilateral oophorectomy),

Exclusion Criteria:

1. Other cancer in the 5 years prior to entry into the trial or concomitant (except in situ cancer of the cervix or basal cell carcinoma of the skin).
2. Presence of cerebral metastasis (s)
3. Prognosis estimated <3 months
4. Presence of a contraindication to bevacizumab (major surgery in the previous 28 days, risk of arterial thrombosis, risk of haemorrhage, deep vein thrombosis without effective anticoagulant therapy or unbalanced anticoagulant therapy)
5. History of grade 4 toxicity to oxaliplatin, irinotecan, 5FU or bevacizumab
6. Persistence of neuropathy greater than a grade 1
7. Hypersensitivity to one of the compounds of the treatments
8. Participation in course or within 30 days prior to entry into the study to another therapeutic trial with an experimental molecule.
9. Demonstration of a DPYD and / or UGT1A1 mutation
10. Unbalanced serious illness, underlying infection that may prevent the patient from receiving treatment
11. Pregnancy (compulsory pregnancy test at baseline), breastfeeding or lack of effective contraception for men and women of childbearing age
12. Psychiatric illness compromising understanding of information or completion of study
13. Patient under tutorship, curatorship or court of justice
14. Inability to sign informed consent or to undergo medical follow-up of the trial for geographical, social or psychological reasons.