Inclusion Criteria:

- Written informed consent from patients who are able to understand the study request

- Histologically confirmed diagnosis of locally advanced rectal adenocarcinoma; ≤12 cm
from the anal margin; T3, operable T4 or TxN+

- Karnofsky PS Index ≥ 70%

- Life expectancy > 6 months

- Adequate bone marrow, liver and renal function: ANC ≥ 1.5 x 10e9/l; Platelets ≥ 100 x
10e9/l; Hb ≥ 9g/dl; INR ≤ 1.5; Bilirubin ≤ 1.5 x ULN; ALT and/or AST ≤ 2.5 x ULN or ≤
5 x ULN (in case of hepatic metastasis); Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x
ULN (in case of hepatic metastasis) or ≤ 10 x ULN (in case of bone metastasis);
Creatinine clearance (Cockcroft-Gault) ≥ 30 ml/min or seric creatinine ≤ 1.5 x ULN

Exclusion Criteria:

- Distant metastases; previous neoplasm during last 5 years or previous infiltrating
neoplasm; previous treatment with radiotherapy or study drugs; recruited for other
clinical trial in 4 weeks before study entry

- Surgery, open biopsy or traumatic injury in 4 weeks before study entry; fine-needle
aspiration in 7 days before study entry; major surgery planned during study

- Previous heart disease or uncontrolled hypertension, previous hemorrhagic diathesis
or coagulopathy; full-dose oral or parenteral anticoagulant or thrombolytic agent
(low-dose warfarin is allowed, INR ≤ 1.5); chronic use of high-dose aspirin
(<325mg/day) or non-steroidal anti-inflammatory treatment

- No integrity of the upper gastrointestinal tract, malabsorption syndrome or unable to
take oral drugs

- Pregnant or lactating patients; SNC disease; allogeneic transplant with
immunosuppressive drugs; bone fracture not healed, wound or severe ulcers;
uncontrolled intercurrent severe infections; previous related-fluoropyrimide SAEs or
DPD deficiency