Inclusion Criteria:

General

- Pathologically confirmed rectal adenocarcinoma

- T3 or T4 or N1 (node ≥1 cm on short axis) adenocarcinoma of the rectum.

- ECOG performance status equal or less than 1

- Male and female patients, aged ≥ 18 years and ≤ 80 years

- Written informed consent

- Adequate haematological, liver, renal function

Resectability

- Patients categorized as having resectable locally advanced cancer

- Favorable general condition

Exclusion Criteria:

Resectability

- Diagnosis of metastatic disease

- Clear indication of involvement of pelvic wall(s), on imaging.

- Peritoneal carcinomatosis, portal vein occlusion, ascites, non-regional lymph nodes

- Histology other than adenocarcinoma

- Obstructed rectal carcinoma without defunctionalizing colostomy

Prior treatment

- Previously undergone treatment for this disease

- Prior chemotherapy for colorectal cancer

- Prior chemotherapy for other malignancies in past 12 months

- Prior radiotherapy other than skin cancer

- Concomitant use of St John's Wort

- Treatment with any other investigational agent

- Current use of full-dose of warfarin for therapeutic

Other conditions

- Confirmed or suspected brain metastases

- History or evidence of CNS disease

- Past or current history of other malignancies

- Clinically significant cardiovascular disease

- Evidence of bleeding diathesis or coagulopathy

- Known hypersensitivity to any of the study drugs

- Serious, non-healing wound, ulcer or bone fracture

- Major surgical procedure or significant traumatic injury within 28 days prior to
treatment

- Disease or condition that contraindicates the use of an investigational drug

- Life expectancy less than 5 years

- Inability or unwillingness to comply with the protocol

- Neuropathy ≥ Gr.2

- History of ulcerative colitis or Crohn's disease

- Pelvic abscess or perforated pelvic carcinoma

Pregnancy / Contraception

- Pregnancy or lactation

- Positive serum pregnancy test within 7 days of starting study treatment