Inclusion Criteria:

• Distant metastatic (TX NX M1) or locally recurrent renal cell carcinoma not amenable to cure by surgical or other means
• Measurable or non-measurable (evaluable) disease either on imaging scan or physical examination
• Pathological confirmation of the diagnosis of renal cell carcinoma either during prior nephrectomy or by biopsy of a primary or metastatic lesion - provision of a paraffin-embedded tissue block to confirm the diagnosis and allow molecular correlate assessment is required.
• ECOG performance status 0 or 1.
• Patients must have an AGC of greater than or equal to 1,500/mm3 and a platelet count of greater than or equal to 100,000/mm3. These tests must be obtained within 28 days of registration.
• Patients must have a calculated or measured creatinine clearance greater than or equal to 40 ml/min obtained within 28 days prior to registration.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male subject agrees to use an acceptable method of contraception for the duration of the study.
• May have been treated with interleukin and/or interferon but must not have had more than one line of prior cytotoxic chemotherapy
• May have had up to one biologic therapy provided they have not had bortezomib or bevacizumab
• May have had up to 2 prior vaccine therapies
• May have been treated with radiation therapy, provided there are measurable or evaluable lesions outside the field of radiation
• May have had radiation provided the patient has recovered from the side effects of the therapy (typically 2 weeks after final fraction) and less than 30% of the total bone marrow has been irradiated

Exclusion Criteria:

• Brain metastases or history of brain metastases
• History of deep vein thrombosis or thromboembolic disease within 1 year or requiring ongoing anticoagulant therapy
• History of stroke or myocardial infarction within six months
• Other major illnesses likely to limit survival including poorly controlled hypertension (BP > 150/100 mmHg) or symptomatic or clinically significant peripheral vascular disease or angina pectoris
• Unstable angina
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• Urine protein:creatinine ratio greater than or equal to 1.0 at screening
• Evidence of bleeding diathesis or coagulopathy.
• Major surgical procedure, open biopsy, significant traumatic injury within 28 days prior to Day 0, or 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 (positive pregnancy test) or lactating; confirmation that female subject is not pregnant by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Inability to comply with study and/or follow-up procedures
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to Day 0
• Serious, non-healing wound, ulcer, or bone fracture
• Neuropathy at baseline > grade 1
• Patient has received other investigational drugs within 14 days before enrollment
• Patient has hypersensitivity to bevacizumab, bortezomib, boron or mannitol