Assessment of the Efficacy of Bevacizumab in Combination With Folfiri as Second-line Treatment in Patients Suffering From an Advanced Inoperable Poorly Differentiated Neuroendocrine Carcinoma of an Unknown or Gastroentero-pancreatic Primary Cancer

Inclusion Criteria:

* Man or woman aged ≥ 18 years old,
* Poorly differentiated neuroendocrine carcinoma (NEC) from a gastrointestinal tract (from esophagus to anal canal) and biliopancreatic primary or an unknown primary cancer, locally advanced and/or metastatic,
* Centralized review of the diagnostic by a consulting pathologist specializing in NET (TENPATH network),
* Recommendation of a second-line chemotherapy after progression, documented using the RECIST criteria v.1.1, and after a first-line chemotherapy treatment by cisplatin (or carboplatin) + etoposide or in the event of progression in the 6 months following the discontinuation of this first-line treatment,
* Recommendation of a second-line chemotherapy for the refractory patient or contraindicated for platinum-etoposide chemotherapy
* Patients presenting at least one measurable target lesion according to the RECIST criteria v.1.1, in an area not previously irradiated,
* General condition ≤ 2 (WHO),
* Patient of child bearing age accepting to use an effective contraception during treatment and until 6 months after the last administration,
* Patient who signed the informed consent form.

Exclusion Criteria:

1. Relating to the tumor, the patient, and previous treatment:

   * Well differentiated neuroendocrine tumor
   * Mixed tumor, except if the NEC component is \> 70%, the patient is eligible,
   * First-line chemotherapy other than cisplatin (or carboplatin) and etoposide,
   * All malignant disease in the three years before randomization, with the exception of basal cell carcinoma or in situ cancer treated for curative purposes,
   * A pregnant or breastfeeding woman,
   * Lack of efficient contraception (for men or women of reproductive age),
   * All medical, geographical, social, and psychological conditions or a legal situation that will not allow the patient to finish the study or sign an informed consent form,
2. Relating to the chemotherapy (Folfiri):

   * Any of the following uncontrolled progressive diseases in the 6 months before randomization: liver failure, renal insufficiency, respiratory distress, congestive heart failure (NYHA III-IV), unstable angina, myocardial infarction, significant arrhythmia,
   * Known deficiency in dihydropyrimidine dehydrogenase,
   * Known Gilbert's syndrome,
   * Total bilirubin level \>1.5x the upper limit of normal (ULN); AST (Aspartate transaminase) and/or ALT (Alanine transaminase) \>5x ULN; TP \<50%;
   * Neutrophils \<1.5x109/l, platelets \<100x109/l, hemoglobin \<9 g/dl,
   * Chronic uncontrolled diarrhea, unresolved intestinal occlusion or subocclusion,
   * History of anaphylactic reaction or known intolerance to atropine (sulfate) or to loperamide or to antiemetics administered in association with Folfiri,
   * All treatment with concomitant anticonvulsive agents, CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), discontinued for at least 7 days,
3. Relating to bevacizumab:

   * Uncontrolled brain metastases (by local treatment),
   * All uncontrolled progressive disease within 1 month prior to randomization: grade 3-4 gastrointestinal bleeding (peptic ulcer, erosive esophagitis or gastritis), infectious disease or intestinal inflammation, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event,
   * Uncontrolled high blood pressure defined as a systolic blood pressure \>140 mmHg or diastolic pressure \>90 mmHg,
   * Patients receiving anticoagulant treatment with an unstable dose of a vitamin K antagonist treatment, and/or having an abnormal INR (\>3) in the four weeks before the randomization,
   * Verified proteinuria above or equal to 1g/24 hours measured from 24 hours of urine if the urinary protein dipstick control is above or equal to 2+,
   * Creatinine clearance (MDRD) \<50 ml/min.
   * Hypersensitivity to the active substance or to any of the excipients.
   * Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.