The primary objective of the NACRE-2 trial is to assess whether the addition of chemotherapy after short-course radiotherapy is more effective than short-course radiotherapy alone in elderly patients with locally advanced rectal cancer. Secondary objectives will assess the efficacy and safety profile of the combination, as well as its effect on patients' quality of life.

Patients will be separated into two groups to receive their assigned treatment:

• Group 1: Short-duration radiotherapy according to standard practice lasting one week, followed by chemotherapy with FOLFOX4s consisting of oxaliplatin (85 mg/m²), folinic acid (400 mg/m²) and 5-Fluoro-Uracil (400 mg/m² administered in hospital, followed by 2400 mg/m² administered over 46 hours at home) every two weeks for 3 months
• Group 2: Short-duration radiotherapy according to standard practice, lasting one week To receive treatment, patients must come to the hospital where, at each visit, the medical team will carry out medical examinations, prior to administering treatment, to assess the patient's general state of health and tolerance to treatment.

A radiological assessment of the disease will be carried out 11 weeks after the end of radiotherapy. Patients whose tumors have not shrunk will undergo surgery to remove them and enter the follow-up phase. Patients whose tumors have shrunk will not undergo surgery, and will enter a surveillance phase. At 21 weeks, patients whose tumors are still present will undergo surgery and enter the follow-up phase. Patients whose tumors have disappeared will remain in a surveillance phase.

During the surveillance or follow-up phases, patients will be monitored in hospital every 3 months (if no progression is observed). In the case of surgery, patients will be monitored every 6 months. The maximum duration of treatment is 3 years.

Comparative interventional prospective phase III, multicenter, randomised, open-label trial evaluating management strategies of locally advanced rectal cancer treatment with SCRT+/-FOLFOX4s+/-TME to optimize chemotherapy use and increase organ preservation in patients ≥ 75 years

Inclusion Criteria:

1. Histologically confirmed diagnosis of adenocarcinoma of the rectum

2. Age ≥75 years

3. WHO performance status 0-1

4. cT3a-b with maximum diameter > 5 cm, T3c-d or cT4 tumor on pretreatment pelvic MRI

5. General condition considered suitable for radical pelvic surgery and a systemic therapy with FOLFOX,

6. Distal part of the tumor ≤10 cm from the anal margin, the measurement done by pelvic MRI

7. Oncogeriatrician approval

8. Adequate biological function defined by:

   1. Neutrophils ≥ 1500/mm3
   2. Platelets ≥ 100 000/mm3
   3. Hemoglobin ≥ 10g/dL
   4. Total bilirubin ≤ 1,5 x ULN
   5. Alkaline phosphatases ≤ 1,5 x ULN
   6. Creatinine clearance >50mL/mn (MDRD)

9. Men must agree to use adequate contraception methods for the duration of study treatment and for within 6 months after completing treatment

10. Patients must be affiliated to a Social Security System (or equivalent).

11. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent

12. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

1. Metastatic disease
2. Other cancer within 3 years prior to rectal cancer diagnosis (except for in situ cancer and basal cell carcinoma of the skin)
3. Non resectable cancer, including extension to prostate or extension to perineal muscles
4. History of pelvic irradiation
5. Contraindication to FOLFOX 4s chemotherapy and/or radiotherapy and/or TME surgery
6. Contraindication to MRI
7. Microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR)
8. Complete or partial Dihydropyrimidine Deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
9. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment
10. Any other serious concomitant disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, heart, kidney, lung, metabolic, or psychiatric disorders).
11. Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization
12. Any psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
13. No prior chemotherapy or surgery for rectal cancer
14. Any serious underlying medical condition (as judged by the investigator) that could impair the ability of the patient to participate in the trial
15. Persons deprived of their liberty or under protective custody or guardianship.
16. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.

Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.