This randomized phase II trial studies how giving a drug called levocetirizine to patients with colorectal cancer affects their tumor response to capecitabine and bevacizumab. Capecitabine is a chemotherapy drug that blocks tumor growth by disrupting DNA and RNA synthesis and repair (cell division and survival). Bevacizumab is a monoclonal antibody that blocks the ability of tumors to grow and spread by inhibiting the growth of blood vessels that feed them. Patients with colorectal cancer can develop a resistance to the effects of bevacizumab. Levocetirizine may decrease tumor resistance to bevacizumab. Giving bevacizumab, capecitabine, and levocetirizine dihydrochloride together may be an effective treatment for refractory colorectal cancer.

Inclusion Criteria:

• Patient must have histologically or cytologically confirmed refractory colorectal cancer (CRC).

• Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam.

• Patient must have documented progressive disease within 3 months of his/her most recent cycle of chemotherapy.

• Patient must be refractory to or intolerant of prior therapy with a fluoropyrimidine, oxaliplatin, irinotecan, and/or anti-angiogenic therapy. Patients with K-RAS wild type tumors must have received an epidermal growth factor receptor (EGFR) inhibitor such as cetuximab or panitumumab.

• Patient must be ≥ 18 years of age.

• Patient must have an ECOG performance status ≤ 2

• Patient must have normal bone marrow and organ function as defined below:

  • Absolute neutrophil count ≥ 1,500/mcl
  • Platelets ≥ 100,000/mcl
  • Total bilirubin ≤ 2.0 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Patients must have adequate renal function prior to chemotherapy defined as serum creatinine ≤ 2.0 mg/dl OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above 2.0

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

• Patient must be able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria:

• Patient must not have a history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Patient must not be receiving any other investigational agents.
• Patient must not have known active brain metastases. Patients with previously treated brain metastases are eligible. Patients with known brain active metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to levocetirizine, capecitabine, bevacizumab, or other agents used in the study.
• Patient must not have known dihydropyrimidine dehydrogenase (DPD) deficiency or severe renal impairment (creatinine clearance below 30 mL/min by Cockcroft and Gault formula) as this would prelude use of capecitabine.
• Patient must not have known proteinuria ≥ 500mg/24 hours.
• Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient must not be pregnant and/or breastfeeding. Patient must have a negative urine pregnancy test within seven days of study entry.
• Patient must not be known to be HIV-positive on combination antiretroviral because of the potential for pharmacokinetic interactions with levocetirizine, capecitabine, and bevacizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Arm A: 4 patients not evaluable for serious adverse event and adverse event collection (2 had unrelated adverse events after enrollment but prior to treatment, 1 withdrew consent after enrollment but prior to treatment, & 1 was found ineligible after enrollment but prior to treatment). Arm B: 1 patient not evaluable for serious adverse event and adverse event collection because of noncompliance after enrollment but before treatment