The purpose of this study is determine the safety of 5-fluorouracil, bevacizumab and erlotinib when administered in combination with external beam radiation therapy(Phase I portion) as well as to begin to collect information about whether this combination treatment is effective in treating(Phase II portion) patients with locally advanced rectal cancer.

• All participants will receive the following drugs: 5-fluorouracil (5-FU) given as a continuous 24-hour infusion; Bevacizumab given intravenously; erlotinib given orally at home. In the Phase I portion, we are looking for the highest dose of erlotinib that can be given safely in combination with the 5-FU, bevacizumab and radiation therapy. Therefore the dose of erlotinib may not be the same for each participant. The dose will increase until we find the highest dose without causing serious or unmanageable side effects.
• Study treatment is given as an outpatient and consists of 14 day cycles with a total of 3 cycles. Patients will be given all three study drugs and radiation therapy on a monday (unless a monday falls on on a holiday). This will be day 1 of the first treatment cycle. 5-FU is given continuously days 1-14. Bevacizumab is given on day 1. Erlotinib will be given on days 1-14. Radiation therapy will be performed on Days 1-5 and 8-12.
• The following tests and procedures will be performed weekly while participants are receiving study treatment: physical examination, measurement of vital signs, height and weight; performance status; blood work, urine sample.
• At the end of treatment the following tests will be performed: physical examination and measurement of vital signs; performance status; blood work; CT scans of chest, abdomen and pelvis. Patients will also be evaluated for surgery at this time. Patients will be followed every three months for the first three years after surgery, then every 6 months for the next two years.

Inclusion Criteria:

• Histologically confirmed primary adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy or colonoscopy
• Clinical T3 or T4 tumors as determined by endoscopic ultrasound and/or rectal MRI
• ECOG performance status of 0-2
• 18 years of age or older
• Creatinine of < 2.0
• Adequate hepatic function
• Adequate hematopoietic function
• Use of effective means of contraception in subjects of child-bearing potential

Exclusion Criteria:

• Evidence of metastatic disease as determined by chest/abdominal/pelvic CT or physical exam
• Prior chemotherapy or radiation therapy for treatment of colorectal cancer
• Prior treatment with 5-FU
• Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor
• Patients must not be receiving any other investigational agent
• Prior malignancy within the last 5 years except for completely excised skin cancer, in situ cervical cancer
• Warfarin anticoagulation
• Co-existent malignant disease
• Current or recent participation in a clinical trial (within 4 weeks from the first day of treatment)
• Pregnancy
• Blood pressure of >150/100 mmHg
• Unstable angina
• NYHA Grade II or greater congestive heart failure
• History of myocardial infarction within 6 months
• History of stroke within 6 months
• Clinically significant peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Presence of central nervous system or brain metastases
• Major surgical procedure, open biopsy, or significant trauma injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the course of the study
• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
• Pregnant or lactating
• Urine protein:creatinine ratio > or equal to one at screening
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0]
• Serious, non-healing wound, ulcer, or bone fracture