Inclusion Criteria:

- Patients with histologically or cytologically confirmed diagnosis of locally advanced
rectal cancer (LARC) at high risk of recurrence (T4, N+, T3N0 with tumor located in
the lower third of the rectum and/or circumferential resection margin (CRM) £5 mm),
or LARC with resectable organ metastasis (M1).

- Age 18 years or older

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

- Life expectancy of at least 12 weeks

- Measurable and/or evaluable (resectable organ metastasis)lesions according to RECIST
criteria

- Neutrophils > 1500 and Platelets > 100,000 /L

- Total bilirubin < or = 1.5 time the upper-normal limits (UNL) of the Institutional
normal values and ASAT (SGOT) and/or ALAT (SGPT) < or = 2.5 x UNL, or < or = 5 x
UNL in case of liver metastases, alkaline phosphatase < or = 2.5 x UNL, or < or = 5
x UNL in case of liver metastases.

- Creatinine clearance > 50 mL/min or serum creatinine < or = 1.5 x UNL

- Urine dipstick of proteinuria < 2+. Patients discovered to have > or = 2+
proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine
collection and must demonstrate < or = 1 g of protein/24 hr.

- Written informed consent.

- Patients must be accessible for treatment and follow up. Patients registered on this
trial must be treated and followed at the participating Center

Exclusion Criteria:

- Prior radiotherapy or chemotherapy for rectal cancer.

- Untreated brain metastases or spinal cord compression or primary brain tumours

- History or evidence upon physical examination of CNS disease unless adequately
treated (e.g., seizure not controlled with standard medical therapy or history of
stroke).

- History of inflammatory bowel disease and/or acute/subacute bowel occlusion

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

- Evidence of bleeding diathesis or coagulopathy.

- Uncontrolled hypertension

- Clinically significant (i.e. active) cardiovascular disease, for example
cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), unstable
angina, New York Heart Association (NYHA) grade II or greater congestive heart
failure, serious cardiac arrhythmia requiring medication

- Current or recent (within 10 days prior to study treatment start) ongoing treatment
with anticoagulants for therapeutic purposes.

- Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications
known to predispose to gastrointestinal ulceration.

- Treatment with any investigational drug within 30 days prior to enrolment.

- Patients with known allergy to Chinese hamster ovary cell proteins, or any of the
components of the study medications

- Other co-existing malignancies or malignancies diagnosed within the last 5 years with
the exception of basal and squamous cell carcinoma or cervical cancer in situ

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to study treatment start, or anticipation of the need for major surgical
procedure during the course of the study.

- Pregnant or lactating women. Women of childbearing potential with either a positive
or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for
at least 12 months to be considered of non-childbearing potential. Sexually active
males and females (of childbearing potential) unwilling to practice contraception
during the study.