zeroentropy's comments

OHTTP is designed for low latency or lightweight applications. A VPN (or MASQUE, to later comments) requires that you do two handshakes before making a request: one with the VPN and one with the server you want to talk to. OHTTP does away with the second and, where where you are making multiple requests, lets the first handshake only occur once (a VPN/MASQUE can do this too).

Now, this has very little to do with what you might trust Firefox or Mozilla to do. OHTTP only provides a degree of anonymity. If you don't want to share the data that is carried in the message, then you might want to disable the request, not the privacy protections that OHTTP provides. Firefox will use OHTTP for different purposes, so you need to look at each in turn.

OHTTP encapsulates a complete request, so the 1-1-1 mapping isn't right. The target can be any resource, but it generally should be on the same host/origin as the gateway. The gateway sees the request and the response, so there are very few cases where you would trust it to handle requests for any URL.