• Histologically confirmed diagnosis of adenocarcinoma of the rectum |
• Distal part of the tumour within 4–12 cm of the anal verge |
• No unequivocal evidence of established metastatic disease (on chest/abdominal/pelvis CT). Patients with equivocal lesions (as determined at MDT) are eligible |
• MRI-evaluated-evaluated locally advanced tumour with the following: |
  • T3 tumours extending (≥4 mm), beyond the muscularis propria N0–N2 |
  • Or tumours (involving or threatening the peritoneal surface) or presence of macroscopic extramural venous invasion (V2 disease) |
  • AND for tumours below the peritoneal reflection, the primary tumour or involved lymph node (on MRI) must be >1 mm from the mesorectal fascia |
• Measurable disease (using RECIST criteria v1.1) |
• WHO performance status 0 – 1 |
• In the opinion of the investigator: |
  ▪ General condition considered suitable for radical pelvic surgery |
  ▪ Candidate for systemic therapy with FOLFOX/FOLFOXIRI plus bevacizumab |
   ▪ Adequate bone marrow, hepatic and renal function: |
   ▪ Haemoglobin ≥80 g/L |
  ▪ ANC ≥2 × 109/L |
  ▪ Platelet count ≥100 × 109/L |
  ▪ ALT or AST ≤1.5 × ULN (upper limit of normal) |
  ▪ ALP ≤1.5 × ULN |
  ▪ Total bilirubin ≤1.5 × ULN |
  ▪ Serum creatinine ≤1.5 × ULN |
  ▪ Creatinine clearance ≥50 mL/min using the Cockcroft–Gault formula (see Appendix 4). If the calculated GFR is below <50 ml/min, 51Cr-EDTA or 99mTc-DTPA clearance test must be carried out demonstrating GFR is ≥50 ml/min |
• INR ≤ 1.1 |
• Urine protein ≤1+ with dipstick or urine analysis. |
  ▪ For proteinuria >1+ or urine protein/creatinine ratio ≥ 1.0, 24-h urine protein should be obtained and the level must be <2 g for eligibility |
• No evidence of established or acute ischaemic heart disease on ECG and normal clinical cardiovascular assessment |
• No known significant impairment of intestinal absorption |
• At least 18 years of age, but not more than 75 years |
• Willing and able to give informed consent, comply with treatment and follow up schedule |