Chemotherapy Followed by Pelvic Reirradiation Versus Chemotherapy Alone as Pre-operative Treatment for Locally Recurrent Rectal Cancer

Inclusion Criteria:

* Signed and dated informed consent
* Age ≥18 years
* LRRC (histologically proven) ≤ 15 cm from the anal verge
* First or second LRRC (histologically proven) ≤ 15 cm from the anal verge
* Previous pelvic irradiation for the primary rectal cancer or primary recurrence (25-50.4Gy)
* No distant metastasis
* Resectable locally recurrent rectal cancer (according to the International consensus, absolute contraindications for resectabililty are bilateral sciatic nerve involvement, circumferential bone involvement, high sacral involvement requiring total sacrectomy; relative contraindications for resectabilty are sciatic notch involvement and encasement external iliac vessels)
* Adequate hematologic function : Hemoglobin ≥ 9 g/dL, leukocytes ≥ 4000/mm3, neutrophil count ≥ 1500/mm3, blood platelets ≥ 100 000/mm3
* Adequate hepatic function : total bilirubin ≤ 1,5 x ULN, ASAT et ALAT ≤ 3 x ULN, alkalin phosphatases ≤ 3 x ULN
* Adequate renal function : creatinine clearance ≥ 30 ml/min
* ECOG performance status \< 2
* Women not sterilized by the first treatment (ovarian transposition) and males (and their female partners) patients agree to use two methods of effective contraception (one of them being a barrier method) during the study, for at least 6 months for men and for women after the last administration of study treatment
* Patient affiliated to a social security system or beneficiary of the same
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

* Recurrent rectal cancer after local excision
* Concomitant cancer or medical history of cancer within 5 years other than cancers treated in situ (cervical carcinoma or basocellular carcinoma or spinocellular carcinoma)
* Contraindication for chemotherapy Contraindication for chemotherapy (refer to Summary of characteristics of the products of the study drugs available at http://base-donnees-publique.medicaments.gouv.fr) or radiotherapy or surgery
* Symptomatic cardiac or coronary insufficiency
* Personal or family history of long QT syndrome congenital
* ECG at screening or baseline (predose) with QT/QTc \> 450 msec (male) or QT/QTc \> 470 msec (female)
* Chronic inflammatory bowel disease and/or bowel obstruction
* Patients with hypocalcemia, hypokalemia, hypomagnesemia.
* Progressive active infection (HIV or chronic hepatitis B or C) or any other severe medical condition that may preclude the delivery of treatment
* Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
* If contraindication to FOLFIRINOX, possibility to administred FOLFOX or FOLFIRI +/-EGFR (Contraindication to oxaliplatin: peripheral neuropathy \> grade 1 (CTCAE grading system v5.0)
* Peripheral neuropathy \> grade 1 (CTCAE grading system v5.0)
* Concomitant treatment with millepertuis, yellow fever vaccine, live attenuated vaccine, phenytoin, warfarin or sorivudine (or chemically equivalent)
* Pregnant or breast-feeding woman
* Persons deprived of liberty or under guardianship or incapable of giving consent
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule, as assessed by investigator