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The paper addresses the heterogeneous fleet vehicle routing problem with three-dimensional (3D) loading constraints (3L-HFVRP), a new practical variant of the combined routing and loading problem. In this problem, the loads consist of a set of three-dimensional, rectangular shaped items. The fleet is composed of heterogeneous vehicles with different weight and space capacities. The objective is to serve all customers by selecting a set of vehicles such that the total transportation cost is minimized. The cost consists of the fixed cost of the selected vehicles and their travel cost. In addition, loading sequence related constraints frequently encountered in realistic applications are respected when loading and unloading the items. To solve this challenging problem, we develop an adaptive variable neighborhood search (AVNS) which utilizes an extreme point based first fit heuristic to find a feasible loading pattern for …