Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.

Bevacizumab dosing is 10 mg/kg on day 1 and day 15 of a 28 days course given IV.

Irinotecan dosing is 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the MTD of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150 mg/m2.

For dose level 0 Temozolomide, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO. Doses will be escalated according to standard phase I dose escalation criteria.

Inclusion Criteria:

• Medulloblastomas, high-grade glioma, low-grade glioma, and ependymoma are eligible. Other central nervous system tumors may be considered for treatment at discretion of investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic pathway tumor.
• The patient should have failed first line therapy and be considered refractory, relapsed, or recurrent. Exceptions are high grade gliomas including brain stem gliomas.
• Age 18 months though age 23 years are eligible for this protocol.
• The patient may have received any of the agents, but not in this combination. Patients will not be eligible if they have received the combination of bevacizumab and IV irinotecan as prior therapy. They will not be eligible if they had progressive disease on any of these agents. Investigator discretion may also be used.
• Bone marrow should be recovered from prior therapy with ANC >1500 and platelets >100,000.
• Serum creatinine should be less than institutional upper limit of norm.
• ALT/AST <3 times normal and bilirubin <1.5 times normal.
• Neurologic symptoms should be stable for 1 week with stable or decreasing doses of steroids.
• Patients should not be pregnant or breast feeding.

Exclusion Criteria:

• Patients with bleeding disorders or on anticoagulants.
• Uncontrolled hypertension.
• Other risks of bleeding determined on individual basis.
• Patients receiving enzyme inducing anticonvulsants.
• Patients with significant cardiac or pulmonary dysfunction that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results.
• For patients receiving bevacizumab, those who have had surgical procedures should not receive bevacizumab within 28 days of a major procedure, 14 days of an intermediate procedure and 7 days of a minor procedure. Lumbar punctures or placement of PICC lines are not considered minor procedures and may occur at any time prior to or during therapy.

Will determine after further data analysis

Two 28 day cycles for each participant