Postoperative Hepatic Arterial Chemotherapy in High-risk Patients as Adjuvant Treatment After Resection of Colorectal Liver Metastases

Inclusion Criteria:

1. Histologically confirmed metastatic colorectal adenocarcinoma,
2. Curative-intent resection (or ablation) R0 of at least 4 CRLM,
3. Preoperative oxaliplatin- and/or irinotecan-based chemotherapy (successively or concomitantly) +/- non experimental biological therapy, e.g., anti-EGFR or antiangiogenic antibody,
4. Confirmed radiological tumor control before surgery (i.e., objective response or stable disease according to RECIST1.1 criteria),
5. WHO performance status of 0 or 1,
6. Age ≥ 18 years,
7. Adequate hematological function: absolute neutrophil count (ANC) \> 2 x 109/L; platelets \> 100 x 10\^\^9/L, hemoglobin (Hb) \> 9 g/dL.
8. Adequate liver function: serum bilirubin \</= 1.5 x ULN;
9. Aminotransferases levels \</= 2.5 ULN (\</= 5 ULN if liver metastases in place), and alkaline phosphatase level ≤ 5 ULN
10. Creatinin clearance ≥ 30 ml/min
11. Informed consent signed by the patient or his/her legal representative.
12. Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). Both men and women (of childbearing potential) who are sexually active must use adequate contraception, during and for at least 6 months post-treatment.

Exclusion Criteria:

1. Extrahepatic metastatic disease (except ≤3 lung nodules (≤10 mm on chest CT scan) deemed amenable to curative-intent resection/ablation),
2. Symptomatic primary tumor requiring urgent surgery, asymptomatic primary colorectal tumor is not a non-inclusion criteria if its
3. Contraindication to fluoropyrimidines or oxaliplatin, as mentioned in the SMPC of investigational medicinal products
4. Known dihydropyrimidine dehydrogenase (DPD) deficiency
5. Disease progression during, or early hepatic relapse (\< 6 months) after the end of, oxaliplatin-based adjuvant chemotherapy following primary tumor resection
6. History of hepatic arterial infusion with any treatment (chemotherapy, radioembolisation),
7. Peripheral neuropathy\> grade 1,
8. History of cancer within 5 years prior to entry into the trial other than adequately treated basal-cell skin cancer or in situ carcinoma of the cervix
9. Concomitant administration of cimetidine
10. Concomitant medications/comorbidities that may prevent the patient from receiving study treatments,
11. Patient already included in another clinical trial with an experimental molecule,
12. Pregnancy or lactation,
13. Patients deprived of liberty or under guardianship,
14. Patients unable to undergo medical monitoring test for geographical, social or psychological reasons.
15. Patients must not have any uncontrolled concurrent illness including, but not limited to, severe active or uncontrolled infection, symptomatic congestive heart failure, unstable, angina pectoris, cardiac arrhythmia, uncontrolled diabetes mellitus or psychiatric illness/social situations that would limit compliance with study requirements resection is planned (REVERSE strategy authorized)