Exchange 2016 does not work through F5, manually configured.

Hello,

it's seems that your monitor don't Work. and therefore your requests to backend are forcibly blocked.

From F5, can you please check backend health:

Connect to F5 CLI, then enter this command

curl -i -k https://1.1.1.2/mapi/healthcheck.htm -H "Host: mapi.domain.com"

1.1.1.2 is one of your exchange backend and mapi.domain.com will be the fqdn of your mapi service.

You will obtain this:

HTTP/1.1 200 OK
Server: Microsoft-IIS/10.0
X-Powered-By: ASP.NET
X-FEServer: servname
Date: Fri, 13 Apr 2018 07:48:07 GMT
Content-Length: 29

normally this url must be reachable and there must be no authentication on it.

You will have the same result for :

/Microsoft-Server-Activesync/healthcheck.htm

/EWS/healthcheck.htm

...