Inclusion Criteria:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective (Phase I Part).
• Patients with histologically confirmed metastatic colorectal cancer, who failed with prior two different chemotherapy regimens (Phase II Part).
• At least one evaluable lesion. Lesions must be evaluated by computerized tomography (CT), magnetic resonance imaging (MRI), or PET scan (Phase I Part).
• At least one measurable lesion by CT or MRI of ≥ 20 mm (if conventional CT scan) or ≥ 10 mm (if spiral CT scan) (Phase II part)
• Karnofsky Performance Status ≥ 60%
• Must be ≥18 years of age.
• Expected survival of at least 3 months for phase I part, and at least 6 months for phase II part.
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing patients are excluded. Sexually active men must also use acceptable contraceptive methods. Pregnant and nursing patients are excluded because the effects of the combination of PHY906 and CPT-11 on a fetus or nursing child are unknown.
• Must be able and willing to give written informed consent.
• Patients must have the following clinical laboratory values:

ANC count ≥ 1,500/ mm3. Platelets ≥ 100,000/ mm3. Serum creatinine ≤ 2x upper limit of normal. Total bilirubin < 1.5x upper limit of normal. Serum calcium < 12.0 mg/dl. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x the upper limit of normal (≤ 5.0 x ULN is acceptable if liver has tumor involvement) Prothrombin Time (PT), activated partial thromboplastin time (aPTT) and INR ≤ 1.5 x ULN or in the therapeutic range if on anticoagulation Hemoglobin ≥ 9 gm/dl (may be corrected by transfusion).

Exclusion Criteria:

• Symptomatic brain metastasis.
• Serious concomitant systemic disorders (e.g., active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
• Unwilling or unable to follow protocol requirements or to give informed consent.
• No treatment with cytotoxic or biologic agents within the 4 weeks prior to beginning treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 4 weeks must have elapsed from any prior surgery, radiation, hormonal or other drug therapy for their cancer.
• Known HIV positivity, as safety in this patient population has not been assessed.
• Presence of metastatic disease that, in the opinion of investigators, would require palliative treatment within 4 weeks of enrollment.
• Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
• Pregnant or breast-feeding women.
• Men and women of childbearing age and potential, who are not willing to use effective contraception.
• Major surgery within the last 4 weeks.
• Patients taking concurrent medications of any kind which are strong inducers or inhibitors of CYP3A4. Patients receiving any of the following will be excluded: ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort.