This is a multicentric randomized phase III trial comparing adjuvant chemotherapy with gemcitabine versus 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (mFolfirinox) in patients with resected pancreatic adenocarcinoma.

STUDY DESIGN/ Evaluation criteria Main criterion: efficacy The main criterion is the disease-free survival at 3 years. Disease-free survival is the time delay between the date of randomization and the date at which the 1st cancer-related event such as local relapse, distant metastasis, a second cancer or death from any cause is observed. Patients without event at the time of anlaysis will be censored at the date of last follow-up visit.

Locoregional relapse is a disease relapse occurring at the site of primary resection, in the pancreas or in the associated regional lymph nodes.

Metastatic relapse is the distant disease recurrence involving any possible sites of relapse (peritoneal, hepatic, pulmonary, and distant lymph nodes).

Secondary criteria Overall and specific survival Overall survival is the time delay between the date of randomization and the patient's death, irrespective of its cause. Patients who are still living at the time of analysis will be censored at the date of last follow-up visit.

Specific survival is the time delay between the date of randomization and the patient's death due to the treated cancer or a treatment-related complication.

Metastasis-free survival Metastasis-free survival is the time delay between the date of randomization and the date of the 1st distant event occurrence (peritoneal, hepatic, pulmonary, and lymph nodes). Loco-regional events will be discarded and patients still living without metastasis at the time of analysis will be censored at the date of last follow-up examination objectively assessing this type of event.

Tolerance Patients evaluable for toxicity must have received at least one course or injection of the treatment.

Inclusion Criteria:

1. Histologically proven pancreatic ductal adenocarcinoma. Intraductal papillary mucinous tumor of the pancreas (IPMT) with invasive components are eligible.
2. Macroscopically complete resection (R0 or R1 resection).
3. Patients aged from 18 to 79 years.
4. WHO performance status 0-1.
5. No prior radiotherapy and no previous chemotherapy.
6. Full recovery from surgery and patient able to receive chemotherapy: adequate oral nutrition of ≥1500 calories per day and free of significant nausea and vomiting.
7. Adequate hematologic function (Absolute neutrophil count ANC ≥1,500 cells/mm³, platelets ≥100 000 cells/mm³ and hemoglobin ≥10 g/L - possibly after transfusion -).
8. Serum total bilirubin ≤1.5 times the institutional upper limit of normal.
9. Creatinine level <130 micromol/L (14.7 mg/L).
10. Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use two medically acceptable methods of contraception (one for the patient and one for the partner) during the study and for 4 months after the last study treatment intake for women and 6 months for men.
11. Interval since surgery between 21 and 84 days.
12. Patient information and signed informed consent.
13. Public or private health insurance coverage.

Exclusion Criteria:

1. Other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cystadenocarcinoma and malignant ampulloma.
2. Metastases (including ascites or malignant pleural effusion).
3. Macroscopic incomplete tumor removal (R2 resection).
4. CA 19-9 > 180 U/ml within 21 days of registration on study.
5. No heart failure or coronary heart disease symptoms.
6. No major comorbidity that may preclude the delivery of treatment or active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes.
7. Pre-existing neuropathy, Gilbert's disease or genotype UGT1A1 * 28 / * 28.
8. Inflammatory disease of the colon or rectum, or occlusion or sub-occlusion of the intestine or severe postoperative uncontrolled diarrhea.
9. Concomitant occurrence of another cancer, or history of cancer except in situ carcinoma of the cervix treated or basal cell carcinoma or squamous cell carcinoma.
10. Fructose intolerance.
11. Persons deprived of liberty or under guardianship.
12. Psychological, familial, sociological or geographical condition potentially. hampering compliance with the study protocol and follow-up schedule.